| Primary | Degree of Lesion Contrast Enhancement | Degree of lesion contrast enhancement is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored up to 5 lesions using image sequences and a 4-point scale (1 - No = Lesion not enhanced; 2 - Moderate = Lesion weakly enhanced; 3 - Good = Lesion clearly enhanced; 4 - Excellent = Lesion clearly and brightly enhanced). | Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI. | Posted | | Mean | Standard Deviation | Scores on a scale | | Up to 20 days | | | | ID | Title | Description |
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| OG000 | Gadoterate 0.1 mmol/kg BW | Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight by single intravenous (IV) injection. | | OG001 | Gadobutrol 0.075 mmol/kg BW | Participants received gadobutrol at a dose of 0.075 mmol/kg body weight by single intravenous (IV) injection. |
| | | Title | Denominators | Categories |
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| Unenhanced | | | Title | Measurements |
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| - OG0000.884± 0.252
- OG0010.863± 0.201
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| | Combined unenhanced/enhanced | | |
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| Difference (gadobutrol minus unenhanced) - (gadoterate minus unenhanced) | Paired t-test | | < 0.0001 | No type I error adjustment for multiple comparisons is needed because tests on all 3 primary efficacy variables must be significant to demonstrate primary efficacy. | Mean Difference (Final Values) | 0.455 | | | 2-Sided | 95 | 0.347 | 0.562 | | | | | Non-Inferiority | The score to evaluate the non-inferiority is calculated for each subject as (combined unenhanced/gadobutrol-enhanced - unenhanced) - 0.8*(combined unenhanced/gadoterate-enhanced - unenhanced). The 95% CI is based on a t-distribution. The non-inferiority for gadobutrol is achieved if the one-sided p-value for "H0: (gadobutrol minus unenhanced) - 0.8*(gadoterate minus unenhanced) ≤ 0" is lower than 0.025. |
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| Primary | Lesion Border Delineation | Lesion border delineation is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded readers scored the delineation of up to 5 lesions using image sequences and a 4-point scale (1 - None = No or unclear delineation; 2 - Moderate = Partial delineation; 3 - Good = Almost clear, but incomplete delineation; 4 - Excellent = Clear and complete delineation). | Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI. | Posted | | Mean | Standard Deviation | Scores on a scale | | Up to 20 days | | | | ID | Title | Description |
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| OG000 | Gadoterate 0.1 mmol/kg BW | Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight by single intravenous (IV) injection. | | OG001 | Gadobutrol 0.075 mmol/kg BW | Participants received gadobutrol at a dose of 0.075 mmol/kg body weight by single intravenous (IV) injection. |
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| Primary | Lesion Internal Morphology | Lesion internal morphology is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored the structure and internal morphology of up to 5 lesions using image sequences and a 3-point scale (1 - Poor = Poor visibility; 2 - Moderate = Partial visibility; 3 - Good = Sufficient visibility) | Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI. | Posted | | Mean | Standard Deviation | Scores on a scale | | Up to 20 days | | | | ID | Title | Description |
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| OG000 | Gadoterate 0.1 mmol/kg BW | Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight by single intravenous (IV) injection. | | OG001 | Gadobutrol 0.075 mmol/kg BW | Participants received gadobutrol at a dose of 0.075 mmol/kg body weight by single intravenous (IV) injection. |
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| Secondary | Number of Lesions Identified | Number of lesions identified (up to 10) detected by 3 blinded Readers. The mean (SD) number lesions in the Average Reader for gadobutrol and gadoterate in the Full Analysis Set was reported below. | Full analysis set (FAS) was used for analysis, which is defined as All subjects for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI. | Posted | | Mean | Standard Deviation | Number of lesions identified | | Up to 20 days | | | | ID | Title | Description |
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| OG000 | Gadoterate 0.1 mmol/kg BW | Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight by single intravenous (IV) injection. | | OG001 | Gadobutrol 0.075 mmol/kg BW | Participants received gadobutrol at a dose of 0.075 mmol/kg body weight by single intravenous (IV) injection. |
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| Secondary | Detection of Malignant Disease | The 3 Blinded Readers had to evaluate if the diagnosis resulting from the combined images was malignant disease or not. Each blinded Reader provided a malignant yes/no response. This was compared to the final diagnosis provided by the Investigator. The majority of Readers (2 or 3 Readers agree) was used to calculate sensitivity, specificity, and accuracy - eg. Final Diagnosis - Malignant (Reader 1-yes, Reader 2-no, Reader 3-yes --- Majority Reader yes) - this would be a match for sensitivity. The percentage of sensitivity, specificity, and accuracy of detection of malignant disease detected by 3 blinded Readers, gadobutrol versus gadoterate (Full Analysis Set) is reported below for Majority Readers. | Full analysis set (FAS) was used for analysis, which is defined as All subjects for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI. | Posted | | Number | | Percentage (%) | | Up to 20 days | | | | ID | Title | Description |
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| OG000 | Gadoterate 0.1 mmol/kg BW | Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight by single intravenous (IV) injection. | | OG001 | Gadobutrol 0.075 mmol/kg BW | Participants received gadobutrol at a dose of 0.075 mmol/kg body weight by single intravenous (IV) injection. |
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| Secondary | Confidence in Diagnosis | Diagnostic confidence detected by 3 blinded Readers, gadobutrol vs gadoterate (Full Analysis Set). Blinded Readers rated their confidence in diagnosis according to a 4-point scale (1 - Not confident; 2 - Somewhat confident; 3 - Confident; 4 - Very confident). Results for the Average Reader are reported below. | Full analysis set (FAS) was used for analysis, which is defined as All subjects for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI. | Posted | | Mean | Standard Deviation | Scores on a scale | | Up to 20 days | | | | ID | Title | Description |
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| OG000 | Gadoterate 0.1 mmol/kg BW | Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight by single intravenous (IV) injection. | | OG001 | Gadobutrol 0.075 mmol/kg BW | Participants received gadobutrol at a dose of 0.075 mmol/kg body weight by single intravenous (IV) injection. |
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| Secondary | Image Quality | Comparison of image quality between gadobutrol and gadoterate detected by 3 blinded Readers (Full Analysis Set). Blinded Readers assessed the image quality of gadobutrol- and gadoterate-enhanced images (randomly assigned as left [L] and right [R] image positions) according to a 5-point scale (1- Image R is worse; 2 - Image R is slightly worse; 3- Image R is similar; 4 - Image R is slightly better; 5 - Image R is better). After unblinding of data, the above codes were translated into the following scale: -2 = Gadobutrol image set is worse ; -1 = Gadobutrol image set is slightly worse ; 0 = Image sets are the same ; 1 = Gadobutrol image set is slightly better; 2 = Gadobutrol image set is better. Results for the Average Reader are reported below. | Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI. | Posted | | Mean | Standard Deviation | Scores on a scale | | Up to 20 days | | | | ID | Title | Description |
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| OG000 | Gadoterate 0.1 mmol/kg BW-Gadobutrol 0.075 mmol/kg BW | Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight (BW) by single intravenous (IV) injection in Study Period 1 and gadobutrol at a dose of 0.075 mmol/kg BW by single IV injection in Study Period 2. |
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| Secondary | Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm | Comparison of contrast enhancement utilizing an overall contrast enhancement estimation algorithm (Full Analysis Set). The exploratory algorithm analyzed the overall enhancement by comparing the axial T1w (longitudinal relaxation time-weighted) enhanced images to the T1w unenhanced images. | Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI. | Posted | | Mean | Standard Deviation | Scores on a scale | | Up to 20 days | | | | ID | Title | Description |
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| OG000 | Gadoterate 0.1 mmol/kg BW | Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight by single intravenous (IV) injection. | | OG001 | Gadobutrol 0.075 mmol/kg BW | Participants received gadobutrol at a dose of 0.075 mmol/kg body weight by single intravenous (IV) injection. |
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| Secondary | Number of Participants With Treatment-emergent Adverse Events | Number of subjects with treatment-emergent adverse events (TEAEs) (Safety Analysis Set). TEAEs are defined as any AEs that increase in intensity or that are newly developed during the TE period for Study Period 1 or Study Period 2, where TE period for Study Period 1 goes from the first study drug administration in Study Period 1 to 24 hours post-injection, and TE period for Study Period 2 from the first study drug administration in Study Period 2 to 24 hours post-injection. | The Safety analysis set (SAF) included all enrolled participants who received at least 1 study treatment administration. | Posted | | Number | | Participants | | From the first study drug administration up to 24 hours post injection | | | | ID | Title | Description |
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| OG000 | Gadoterate 0.1 mmol/kg BW | Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight by single intravenous (IV) injection. | | OG001 | Gadobutrol 0.075 mmol/kg BW | Participants received gadobutrol at a dose of 0.075 mmol/kg body weight by single intravenous (IV) injection. |
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| Post-Hoc | Comparison of Degree of Lesion Contrast Enhancement Detected by Blinded Readers for Combined Image Sets - Equivalence Test | Comparison of degree of lesion contrast enhancement detected by blinded Readers for combined image sets - Equivalence Test (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored up to 5 lesions using image sequences and a 4-point scale (1 - No = Lesion not enhanced; 2 - Moderate = Lesion weakly enhanced; 3 - Good = Lesion clearly enhanced; 4 - Excellent = Lesion clearly and brightly enhanced). | Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI. | Posted | | Mean | Standard Deviation | Scores on a scale | | Up to 20 days | | | | ID | Title | Description |
|---|
| OG000 | Gadoterate 0.1 mmol/kg BW | Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight by single intravenous (IV) injection. | | OG001 | Gadobutrol 0.075 mmol/kg BW | Participants received gadobutrol at a dose of 0.075 mmol/kg body weight by single intravenous (IV) injection. |
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| Post-Hoc | Comparison of Border Delineation Detected by Blinded Readers for Combined Image Sets - Equivalence Test | Comparison of border delineation detected by blinded Readers for combined image sets - Equivalence Test (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored the delineation of up to 5 lesions using image sequences and a 4-point scale (1 - None = No or unclear delineation; 2 - Moderate = Partial delineation; 3 - Good = Almost clear, but incomplete delineation; 4 - Excellent = Clear and complete delineation). | Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI. | Posted | | Mean | Standard Deviation | Scores on a scale | | Up to 20 days | | | | ID | Title | Description |
|---|
| OG000 | Gadoterate 0.1 mmol/kg BW | Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight by single intravenous (IV) injection. | | OG001 | Gadobutrol 0.075 mmol/kg BW | Participants received gadobutrol at a dose of 0.075 mmol/kg body weight by single intravenous (IV) injection. |
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| Post-Hoc | Comparison of Internal Morphology Detected by Blinded Readers for Combined Image Sets - Equivalence Test | Comparison of internal morphology detected by blinded Readers for combined image sets - Equivalence Test (Full Analysis Set). Results are presented as the average Reader score. Blinded Readers scored the structure and internal morphology of up to 5 lesions using image sequences and a 3-point scale (1 - Poor = Poor visibility; 2 - Moderate = Partial visibility; 3 - Good = Sufficient visibility). | Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI. | Posted | | Mean | Standard Deviation | Scores on a scale | | Up to 20 days | | | | ID | Title | Description |
|---|
| OG000 | Gadoterate 0.1 mmol/kg BW | Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight by single intravenous (IV) injection. | | OG001 | Gadobutrol 0.075 mmol/kg BW | Participants received gadobutrol at a dose of 0.075 mmol/kg body weight by single intravenous (IV) injection. |
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